Stents are known in the art. They are typically formed of a cylindrical metal mesh that can expand when pressure is internally applied or when self-expanding metals are employed. Stents can be formed by cutting a pattern from metal tubes or flat sheets of metal that are later folded and formed into tubular stents, or alternatively by forming wire or metal mesh strips wrapped into a tubular shape.
As described in U.S. Pat. No. 4,776,337 to Palmaz, the cylindrical metal mesh shape is produced by laser cutting a thin walled metal tube. The laser cuts away all but the lines and curves of the mesh.
The method of U.S. '337 is applicable for relatively large mesh shapes and for meshes whose lines are relatively wide. However, for more delicate and/or intricate shapes, the spot size of the laser is too large.
Stents have been coated with various compounds and therapeutic agents to enhance their effectiveness, for example, to facilitate the acceptance of the stent into a blood vessel lumen or to facilitate the delivery of therapeutic agents to a target site within a blood vessel. Such drug coated stents have been used in recent years to attempt to reduce the occurrence of restenosis. Restenosis is a common complication that may arise following implantation of vascular stents. Restenosis is a response to the trauma of stent implantation involving scar tissue formation that reduces vessel lumen diameter and may result in recurrence of vessel occlusion or critical narrowing. To avoid the need for further revascularization procedures, which can increase trauma and risk, stents have been designed that deliver beneficial agents to the vessel lumen to prevent or minimize the restenosis problem.
Various methods have been employed to apply coatings to stents. For example, the cylindrical surface of a finished stent may be sprayed with a coating substance or a spinning cylindrical stent may be dipped into a coating solution to achieve the desired coating. See, e.g., U.S. Pat. No. 5,980,972 to Ding et al.
U.S. Pat. No. 6,984,411 to Palasis et al. describes a method for applying a coating to stents while rolling the stents about their longitudinal axis, where the stents are loaded onto rotating holders affixed to a conveyor, and the conveyor carries the rotating stents and holders through a coating applicator one or more times.
During the manufacture of coated stents, care must be taken to ensure that the coating is uniformly applied to the stent surface. A disadvantage of these prior stent coating processes is that uniformity of stent coating is difficult to achieve when spraying the cylindrical surface of a finished stent. These prior stent coating processes also do not allow for the differential treatment of the luminal side of the stent and the vessel wall side of the stent.
A further disadvantage of currently available coating methods of stents is that the coating is made on both the luminal side and vessel wall side of the stent. Not having the ability to provide differential treatment of the luminal and vessel sides of the stent may limit potential applications of the coated stent.
A further disadvantage is that the desired ratio between coating on both surfaces, whether equal or not, is hard or impossible to control. A further disadvantage of existing processes is their inherent slow pace that limits capacity and cost efficiency. A still further disadvantage of coated stents is that coatings can sometimes crack and peel at portions of the stent that bend or deform during crimping or during expansion of the stent.
Thus, there remains a need in the art to have a process of uniformly coating stents, providing a coating having differential treatment of the luminal side of the stent and the vessel wall side of the stent, and coating discrete portions of the stent. It is also desirable for such process to be substantially faster and more cost efficient.
In alternative approaches to enhancing stent effectiveness, stents have been designed with openings or drug depots built into the metal mesh containing a beneficial agent, or made from a porous metal which is loaded with one or more drugs. For example, as described in U.S. Pat. No. 7,179,289 to Shanley, stents may be designed with a plurality of openings or recesses, for example by laser drilling, and filled with various therapeutic agents. The openings or recesses are preferably located in inflexible portions or non-expanding members of the stent. Filling of the openings may proceed by masking the inside of the tubular structure (and optionally the outer surface of the stent structure), spraying the therapeutic agent onto the stent (or dipping the stent), optionally spinning the stent to produce even distribution of the drug composition, and then, where the external surface is not masked, removing the residual drug composition from the stent structure. See U.S. Pat. No. 7,163,555 to Dinh; see also, U.S. Pat. No. 7,060,093 to Dang. Porous metal stents having a desired pore size in the metal structure are fabricated from one or more powdered metals which are pressure-cast into a stent-like form or into sheets or tubes from which the stents are produced, as described in U.S. Pat. No. 6,253,443 to Johnson. The porous metal is impregnated with the drugs to be released therefrom by dipping or soaking in the medium containing the drug.
The porous metal stents and drug depot stents deliver beneficial agents, such as pharmaceutical compounds, without increasing the effective wall thickness or impacting expansion properties of the stent. While these stents thereby overcome some of the problems associated with coated stents or membrane-covered stents, they are beset with disadvantages of their own. For example, existing processes for filling the openings or depots are inefficient, because of the inherent slow pace of the multi-step process of capping, masking, spraying/dipping and removing unwanted drug coating from stent elements, which limits capacity and cost efficiency, and wastes therapeutic agent associated with the coating/removal process of filling the openings. The filling process also can lead to unacceptable variations in quality between stents and within a stent, for example, residual drug composition on the stent frame due to incomplete removal, and dripping and/or uneven volume within an opening because of gravitational effects, as the tubular stent is rotated during the filing process. Another limitation is the lack of continuous control on drug load and the kinetics of its release with the difficulty or even lack of possibility to achieve adequate doses and adequate release kinetics simultaneously for different drugs.
Accordingly, there is a need in the art for a drug delivery stent and fabrication method that overcomes one or more of the above-cited disadvantages in the art.